This renewal of a program project application focuses on the molecular basis of behavior and neuronal function in two genetically tractable model organisms: Drosophila melanogaster and C. elegans. A subtheme is the behavioral and neuronal control of gene expression, which also relies on state-of-the-art microarray technology. In Project 1 (Rosbash and Hall), the Drosophila circadian clock will be further investigated. The goal is to identify new rhythm genes and new clock-controlled genes, by genetic and biochemical means. The possibility of circadian clocks in C. elegans and yeast will also be addressed. Project 2 (White and Rosbash) will focus on the Drosophila gene ELAV. Its protein product ELAV has effects on 3' end formation as well as neuronal splicing. The goals include the elucidation of the biochemical mechanisms that underlie ELAV-mediated pre-mRNA processing in neurons. They also include the identification of direct and indirect targets of ELAV. Project 3 (Griffith) will analyze the contribution of CaMKII to courtship conditioning in flies. The full extent of the adult circuit will be determined, and the contribution of CamKII modulation of Eag potassium channel excitability will be tested. The developmental role of CaMKII in the assembly of the neuronal circuitry will be analyzed, and the sensitive cell groups defined. To determine the temporal pattern of kinase activation, genetically based sensors will measure the real time-activation of CaMKII and PKA in neurons of intact behaving animals. Project 4 (Welte and White) will study the role of the cytoplasmic dynein intermediate chain (Cdic) in specific neuronal functions. It will also determine the extent to which nuclear migration and axonal transport rely on the same components of the dynein transport machinery. Finally, microarrays will be used to determine how nuclear positioning affects gene expression? Project 5 (Sengupta) will address the contribution of signal transduction